Dysmenorrhea is a common gynecological condition in women, often attributed to excessive prostaglandin production, significantly impacting daily activities. Papaya leaves, known for their medicinal properties, are a chosen herbal remedy, albeit with a bitter taste, necessitating combination with pineapple fruit. This study aimed to assess the effectiveness of a combination of papaya leaf extract and pineapple fruit as an alternative treatment for primary dysmenorrhea. In an experimental research design employing the posttest-only control group, 32 male mice were divided into seven groups, injected with acetic acid as a pain inducer, and their writhing responses were recorded for 45 minutes at 15-minute intervals. Data analysis using the ANOVA test revealed significant differences in the number of writhing responses in mice (p <0.05) compared to the positive control group, followed by the Duncan test. The percentage of analgesic protection was as follows: mefenamic acid (61.01%), pineapple fruit extract (62.78%), papaya leaf extract (63.39%), a combination of pineapple and papaya leaf extracts with a dose ratio of 3:1 (73.21%), 2:2 (47.32%), and 1:3 (37.78%). In conclusion, the combination of pineapple extract and papaya leaves in a dose ratio of 3:1 demonstrated the most effective pain reduction.